The project proposes to investigate the pathogenetic mechanism of orofacial herpes simplex virus (HV) infections in small experimental animals and to develop a reproducible model for recurrent herpetic infections. The role of immune serum, immuno-competent cells and interferon in the establishment and maintenance of acute and latent HSV infection in sensory ganglia will be studied. The ability of antiviral drugs to control herpetic infections, and especially their effectiveness to prevent the establishment of latent ganglionic infections will be evaluated. Attempts will be made to select drug resistant HSV mutants, and to characterize the therapeutic response to various antiviral drugs of experimental infections induced by these mutants. The resistance to reinfection of mice surviving untreated and drug-treated primary infections will also be investigated. An important question which we shall try to answer, pending the development of a suitable animal model, is whether, during recurrences, the information for virus synthesis persists at the site of the latent infection or is the entire information channeled to the site of recurrences and latency is maintained through successive reinfection of the ganglia.